This invention relates generally to methods, devices and agents for the removal of nucleophilic toxins present in tobacco and tobacco smoke. Nucleophilic toxins are removed by the passage of tobacco smoke or air containing tobacco smoke through a nucleophilic-toxin-removing filter device. Agents may also be incorporated into smoking and smokeless tobacco to prevent volatilization and absorption, respectively, of nucleophilic toxins. Dosimetry of nucleophilic tobacco combustion products is used to monitor toxin exposure.
Tobacco smoke is a complex mixture which includes numerous chemical compounds and particulates which to a major extent are responsible for both the enjoyment of smoking and the dangers to health in so doing. Use of tobacco products, especially smoking, is associated with increased incidence of lung and other types of cancer, emphysema, and cardiovascular disease. Less lethal adverse effects such as tooth discoloration and facial wrinkling also occur. Among the many compounds present in tobacco smoke are the purported addictive component nicotine, compounds responsible for flavor, and those either proven harmful or believed to be harmful to human health. Tobacco smoke contains chemical toxins such as carbon monoxide and hydrogen cyanide, and known carcinogens such as formaldehyde and hydrazine. Specific compounds in tobacco smoke may fall into more than one of these categories, such as those responsible for flavor. Methods for reducing the exposure of smokers to these toxic compounds without affecting the flavor of smoke have been sought for many decades.
The harmful effects of tobacco use, and principally cigarette smoking, derive from the delivery to the body of toxic compounds present in tobacco and volatilized during its combustion, as well as those formed as a result of combustion. These include gaseous compounds, such as carbon monoxide, hydrogen cyanide, ammonia, and formaldehyde, and others that are volatilized in tobacco smoke, such as benzene, acrolein, hydrazine, and aniline. Collectively, the material which may be condensed from tobacco smoke is known as tar. Several compounds in smoke and tar are classified as carcinogens: benzene, 2-naphthylamine, 4-aminobiphenyl, and the radioactive element polonium-210. Others are considered probable human carcinogens, such as formaldehyde, hydrazine, N-nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosopyrrolidine, benzo[a]pyrene, N-nitrosodiethanolamine, and cadmium. Further compounds in tobacco smoke have been proven to be animal carcinogens. While the carcinogenic potential of these tobacco smoke components has never been tested directly in humans, a cause-and-effect relationship between smoking and the aforementioned adverse effects has been strongly established through epidemiologic studies.
Numerous methods and devices to reduce or remove toxic components from tobacco and tobacco have been proposed and constructed. In general, a porous filter is provided as a first line trap for harmful components, interposed between the smoke stream and the mouth. This type of filter, often composed of cellulose acetate, both mechanically and by adsorption, traps a certain fraction of the tar present in smoke. This type of filter is present on most cigarettes available, yet it allows a significant amount of harmful compounds to pass into the mouth. Epidemiological data connects use of filtered cigarettes with adverse health effects.
An improvement in the effectiveness afforded by a mechanical-type filter such as those described above may be provided by including means for chemically trapping disagreeable and harmful components present in smoke. For example, U.S. Pat. No. 5,076,294 provides a filter element containing an organic acid, such as citric acid, which reduces the harshness of the smoke. A significant body of art focuses on removing formaldehyde, a prevalent component of tobacco smoke with an established and adverse toxicological profile. U.S. Pat. No. 4,300,577 describes a filter comprising an absorptive material plus an amine-containing component which removes aldehydes and hydrogen cyanide from tobacco smoke. U.S. Pat. No. 5,009,239 describes a filter element treated with polyethyleneimine modified with an organic acid, to remove aldehydes from tobacco smoke. U.S. Pat. No. 5,850,840 describes the stabilizing of early glycosylation products in tobacco and tobacco smoke by reaction with compounds such as acetaldehyde. U.S. Pat. No. 4,246,910 describes a filter impregnated with alkali ferrate compounds, or activated carbon or alumina impregnated with potassium permanganate, for removing hydrogen cyanide from tobacco smoke. Control of the delivery of tar, nicotine, formaldehyde and total particulate matter was afforded by a filter element containing zinc thiocyanate, sarcosine hydrochloride, zinc chloride, ferrous bromide, lithium bromide, or manganese sulfate, as describe in U.S. Pat. No. 4,811,745. Inclusion of L-ascorbic acid in a filter material to remove aldehydes is disclosed in U.S. Pat. No. 4,753,250. U.S. Pat. No. 5,060,672 also describes a filter for specifically removing aldehydes, such as formaldehyde, from tobacco smoke by providing a combination of an enediol compound, such as dihydroxyfumaric acid or L-ascorbic acid, together with a radical scavenger of aldehydes, such as oxidized glutathione or urea, or a compound of high nucleophilic activity, such as lysine, cysteine, 5,5-dimethyl-1,3-cyclohexanedione, or thioglycolic acid. U.S. Pat. No. 5,706,833 describes a wet-disintegrable filter rod comprising certain water-soluble polymers which serve as disintegrable adhesives.
As used throughout this application, the terms nucleophile and nucleophilic refer to a negative ion or neutral molecule, such as an amino group or primary or secondary amine, that brings an electron pair into a chemical reaction with another molecule or positive ion, called an electrophile, which is capable of accepting the electron pair, such as an active carbonyl group. Nucleophilic compounds will chemically react with compounds bearing active carbonyl groups, such as aldehydes, anhydrides, activated ketones, and active esters.
Smokeless tobacco includes tobacco products which are used by methods other than smoking, for instance, as snuff and chewing tobacco. Toxic products present in tobacco also enter the body by these methods of using tobacco which do not involve combustion, and these products are also associated with numerous adverse sequelae of tobacco use.
Contrary to the above-cited prior art in which nucleophilic compounds incorporated in a filter were used to trap aldehyde-type toxins in tobacco smoke, it has been discovered that the nucleophilic toxins present in tobacco and tobacco smoke may be removed from tobacco and tobacco smoke by agents, or filters derivatized with chemical moieties comprising these agents, which chemically trap nucleophilic compounds. Tar, mutagens, and known carcinogens present in tobacco and tobacco smoke may be effectively removed by these agents or filters comprising these agents which chemically traps nucleophilic toxins. Furthermore, agents which trap nucleophilic toxins may be incorporated into air filters to remove tobacco-derived toxins from room air, to reduce exposure to second-hand (sidestream) smoke.
In its broadest aspect, the present invention is directed to a method for reducing the level of nucleophilic toxins present in mainstream tobacco smoke by passing mainstream tobacco smoke through a filter element capable of removing nucleophilic toxins present in the smoke, the filter element comprising a polymer derivatized with aldehydic groups. In a preferred embodiment, the smoke retains desirable flavor components after passage through said filter. The polymer may be, by way of non-limiting example, dialdehyde starch, dialdehyde cellulose, periodate-oxidized cellulose, periodate-oxidized starch, periodate-oxidized agarose, periodate-oxidized partially-acetylated cellulose, or combinations thereof. In a preferred embodiment, the toxin-removing agent is dialdehyde starch.
In another aspect of the invention, a method is provided for reducing the level of nucleophilic toxins present in mainstream tobacco smoke by passing the mainstream tobacco smoke through a filter element capable of removing nucleophilic toxins present in the smoke, the filter element comprising a non-polymeric aldehyde agent such as adenosine dialdehyde, inosine dialdehyde, o-phthaldialdehyde, ethylenedioxybis(3-benzaldehyde), and combinations thereof. In a preferred embodiment, the smoke retains desirable flavor components after passage through the aforementioned filter.
In yet another aspect of the invention, a method for reducing the level of nucleophilic toxins present in mainstream tobacco smoke is provided by passing the mainstream tobacco smoke through a filter element capable of removing nucleophilic toxins present in the air, the filter element comprising one or more agents such as but not limited to activated ketones, non-polymeric anhydrides, active esters, or hematein. In a preferred embodiment, the smoke retains desirable flavor components after passage through the filter. By way of non-limiting examples of the foregoing agents, activated ketone toxin-removing agents include xcex1-dicarbonyl compounds, xcex2-dicarbonyl compounds, xcex3-dicarbonyl compounds, and xcex1,xcex2-unsaturated ketones. xcex1-Dicarbonyl toxin-removing agents include camphorquinone, ninhydrin, phenylglyoxal, alloxan, and combinations thereof. xcex2-Carbonyl toxin-removing agents include 5,5-dimethyl-1,3-cyclohexanedione, dibenzoylmethane, and the combination thereof. xcex3-Carbonyl toxin-removing agent include hydrindantin, succinylphenone, and combinations thereof. xcex1,xcex2-Unsaturated ketone toxin-removing agents include 1,2-dibenzoylethylene, curcumin, dicinnamalacetone, and combinations thereof. Non-polymeric anhydride toxin-removing agents include 2-dodecen-1-ylsuccinic anhydride, bicyclo(2,2,2)oct-7-ene-2,3,5,6-tetracarboxylic dianhydride, diethylenetriaminepentaacetic anhydride, ethylenediaminetetraacetic dianhydride, (+)-diacetyl-1-tartaric anhydride, and combinations thereof. Active ester toxin-removing agents include bicyclo(2,2,2)oct-7-ene-2,3,5,6-hydroxysuccinimide ester, N-xcex1-t-butoxycarbonyl-L-alanine-N-hydroxysuccinimide ester, N-xcex1-t-butoxycarbonyl-L-glutamic-xcex1-benzyl ester-xcex3-N-hydroxysuccinimide ester, xcex5-t-butoxycarbonyl-aminocaproic acid N-hydroxysuccinimide ester, N-hydroxysuccinimidyl-activated agarose, 6-aminohexyl N-hydroxysuccinimide ester-activated agarose, and combinations thereof.
In still yet a further aspect of the invention, a device for reducing the level of toxins present in air containing mainstream tobacco smoke is provided wherein said device comprises a filter element through which the mainstream tobacco smoke passes, the filter element capable of removing nucleophilic toxins present in the smoke, the filter element comprising a polymer derivatized with aldehydic groups. In a preferred embodiment, the smoke after passage through the filter element of the device retains desirable flavor components. Suitable polymers include but are not limited to dialdehyde starch, dialdehyde cellulose, periodately oxidized cellulose, periodate-oxidized starch, periodate-oxidized agarose, periodate-oxidized partially-acetylated cellulose, and combinations thereof. Preferably, the toxin-removing agent is dialdehyde starch.
In a further aspect, the present invention is directed to a device for reducing the level of toxins present in mainstream tobacco smoke wherein the device comprises a filter element through which mainstream tobacco smoke passes, the filter element capable of removing nucleophilic toxins present in the smoke, said filter element comprising a non-polymeric aldehyde agent such as but not limited to adenosine dialdehyde, inosine dialdehyde, o-phthaldialdehyde, ethylenedioxybis(3-benzaldehyde), and combinations thereof. In a preferred embodiment, the smoke retains desirable flavor components after passage through the filter.
In a further embodiment, a device is provided for reducing the level of toxins present in mainstream tobacco smoke wherein the device comprises a filter element through which mainstream tobacco smoke passes, the filter element capable of removing nucleophilic toxins present in said smoke, said filter element comprising an agent or agents such as activated ketones, non-polymeric anhydrides, active esters, hematein, and combinations thereof. In a preferred embodiment, the smoke retains desirable flavor components after passage through the filter. Activated ketone toxin-removing agent include xcex1-dicarbonyl compounds, xcex2-dicarbonyl compounds, xcex3-dicarbonyl compounds, and xcex1,xcex2-unsaturated ketones. Non-limiting examples of xcex1-dicarbonyl toxin-removing agents include camphorquinone, ninhydrin, phenylglyoxal, alloxan, and combinations thereof. Non-limiting examples of xcex3-carbonyl toxin-removing agents include hydrindantin, succinylphenone, and combinations thereof. Non-limiting examples of xcex1,xcex2-unsaturated ketone toxin-removing agents include 1,2-dibenzoylethylene, curcumin, dicinnamalacetone, and combinations thereof. Non-limiting examples of non-polymeric anhydride toxin-removing agents include 2-dodecen-1-ylsuccinic anhydride, bicyclo(2,2,2)oct-7-ene-2,3,5,6-tetracarboxylic dianhydride, diethylenetriaminepentaacetic anhydride, ethylenediaminetetraacetic dianhydride, (+)-diacetyl-1-tartaric anhydride, and combinations thereof. Active ester toxin-removing agents include but are not limited to bicyclo(2,2,2)oct-7-ene-2,3,5,6-hydroxysuccinimide ester, N-xcex1-t-butoxycarbonyl-L-alanine-N-hydroxysuccinimide ester, N-xcex1-t-butoxycarbonyl-L-glutamic-xcex1-benzyl ester-xcex3-N-hydroxysuccinimide ester, xcex5-t-butoxycarbonyl-aminocaproic acid N-hydroxysuccinimide ester, N-hydroxysuccinimidyl-activated agarose, 6-aminohexyl N-hydroxysuccinimide ester-activated agarose, and combinations thereof.
The foregoing devices used to filter mainstream tobacco smoke in a tobacco smoke-generating device or in a tobacco smoke-containing environment may be provide in a form such as but not limited to a cigarette, free-standing cigarette filter, pipe, cigar, air ventilation filter, gas mask, or face mask.
The filter element of the devices and methods incorporating the devices of the invention may incorporate a granular form of an agent described herein, the granular form prepared for example by methods described hereinbelow.
In yet still another aspect of the invention, a method is provided for preventing the absorption into the body of nucleophilic toxins present in smokeless tobacco by incorporating into the tobacco an agent capable of binding nucleophilic toxins present therein, the agent including but not limited to those described hereinabove, such as a polymer derivatized with aldehydic groups, adenosine dialdehyde, inosine dialdehyde, o-phthaldialdehyde, ethylenedioxybis(3-benzaldehyde), activated ketones, anhydrides, active esters, hematein, and combinations thereof.
In another aspect, the invention is directed to a method for reducing the level of nucleophilic toxins present in mainstream tobacco smoke derived from a tobacco-containing smoking device while retaining desirable flavor components by incorporating into the tobacco of the device an agent capable of binding nucleophilic toxins present in the tobacco, the agent one or a combination of those described hereinabove.
The invention herein is also directed to a device for monitoring the level of nucleophilic toxins in contact therewith comprising a nucleophilic-toxin-binding filter, means for detecting a change in the physicochemical properties of the filter which is related to the level of nucleophilic toxins bound to said filter, and means for indicating the level of nucleophilic toxins bound to the filter.
It is yet a further object of the invention to provide reduction in exposure of individuals to the toxic components in tobacco and tobacco smoke without reducing the enjoyment of using the tobacco products.
It is yet another object of the present invention to provide a dosimetry device utilizing the agents of the present invention to provide an indication of the level of exposure to nucleophilic toxins present in the environment.